Aspirin, But Not Clopidogrel, Reduces Collateral Conductance in a Rabbit Model of Femoral Artery Occlusion
Imo E. Hoefer, MD, PhD*, , ,*,
Sebastian Grundmann, MD*, ,
Stephan Schirmer, MD*, ,
Niels van Royen, MD, PhD ,
Benjamin Meder, MD*,
Christoph Bode, MD*,
Jan J. Piek, MD, PhD and
Ivo R. Buschmann, MD*,||
* Research Group for Arteriogenesis, Department of Cardiology, University of Freiburg, Freiburg, Germany
Perfusion Technologies GmbH, Freiburg, Germany
Department of Experimental Cardiology, UMC, University of Utrecht, Utrecht, the Netherlands
Department of Cardiology, AMC, University of Amsterdam, Amsterdam, the Netherlands
|| Humboldt University, Center for Cardiovascular Research, Charité, Berlin, Germany.

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Figure 1 Postmortem angiograms one week after femoral artery ligation. Neither aspirin nor clopidogrel treatment affected angiographic appearance and number of collateral arteries.
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Figure 2 Collateral conductance measurements for the total tissue mass that depends on the collateral network seven days after femoral artery ligation (open bars). Aspirin treatment significantly reduced collateral conductance, whereas clopidogrel treatment did not functionally affect arteriogenesis (saline: 50.7 ± 1.9 ml/min/100 mm Hg; clopidogrel: 49.5 ± 2.4 ml/min/100 mm Hg; aspirin: 32.6 ± 1.6 ml/min/100 mm Hg). The contralateral hind limb that was subjected to acute occlusion of the femoral artery served as an internal control (solid bars).
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Figure 3 (A) Staining for cyclooxygenase (COX)-1 (red) indicated expression in the endothelium of quiescent arteries in the control hind limb. In proliferating collateral arteries, transmigrated CD11b-positive leukocytes (green) reveal a strong positive stain and serve as additional sources of COX-1. (B) Immunohistological staining for vascular smooth muscle cells (green) and accumulating monocytes/macrophages (red) in the surrounding tissue of the proliferating collateral arteries (first two columns). Proliferating cells (third column) stained for the Ki-67 antigen (red) are mainly localized in the media of the growing vessels. Vascular smooth muscle cells are stained green and nuclei appear blue. Aspirin treatment significantly reduced leukocyte migration and proliferation; clopidogrel-treated animals showed comparable results as saline-treated animals.
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